Application of dimethyl fumarate (DMF) in aspects of regulating tumor metabolism and inhibiting tumor growth

A technology of dimethyl fumarate and DMF, which is applied in the fields of biotechnology and medicine, can solve the problems of depriving immune cells of nutrients, and achieve the effects of improving T cell reactivity, enhancing efficiency, and reducing inhibition

Active Publication Date: 2020-08-25
WUHAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, tumor cells rapidly consume glucose and amino acids, depriving immune cells of nutrients to maintain effector functions

Method used

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  • Application of dimethyl fumarate (DMF) in aspects of regulating tumor metabolism and inhibiting tumor growth
  • Application of dimethyl fumarate (DMF) in aspects of regulating tumor metabolism and inhibiting tumor growth
  • Application of dimethyl fumarate (DMF) in aspects of regulating tumor metabolism and inhibiting tumor growth

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 Utilizes DMF to suppress the proliferation process of various tumor cells

[0024] MTT assay is used to measure the inhibitory effect of different concentrations of DMF on the proliferation of 4T1 breast cancer cells and CT26 colon cancer cells, including the following steps:

[0025] (1) Take the cells in the logarithmic growth phase, and count them with a hemocytometer after digestion;

[0026] (2) Add 1×10 to the 96-well plate 4 1 cell, 100 μL per well; add different concentrations of DMF for 24 h or 48 h after adherence to the wall for 2 to 4 h;

[0027] (3) Add 10 μL of CCK8 reagent to each well, and detect the absorbance of each well at 450 nm with a microplate reader after 24 or 48 hours;

[0028] (4) Draw a standard curve and calculate the inhibitory effect of different concentrations of DMF on tumor cell proliferation.

[0029] According to the DMF obtained by the above-mentioned method, the inhibitory effect on tumor cell proliferation is as fo...

Embodiment 2

[0030] Example 2 Using DMF to Regulate the Metabolic Process of Various Tumor Cells

[0031] 4T1 breast cancer cells and CT26 colon cancer cells were treated with different concentrations of DMF to detect the release level of extracellular lactic acid and the levels of intracellular ATP and ROS.

[0032] Lactic acid release assay:

[0033] will be 5×10 5 Tumor cells were seeded in each well of a 6-well plate and treated with DMF for 48 hours. The cell culture medium was collected, and the lactic acid content was detected with a lactic acid detection kit.

[0034] Intracellular ATP level detection:

[0035] will be 5×10 5 Tumor cells were seeded in each well of a 6-well plate and treated with DMF for 48 hours. The cell culture medium was collected, and the ATP content was detected with an ATP detection kit.

[0036] Intracellular ROS level detection:

[0037] (1) Plate the day before the test, plant a certain density of cells in a 6-well plate, and treat with DMF for 48 ...

Embodiment 3

[0044] Example 3 Use of DMF to inhibit tumor growth in tumor-bearing mice

[0045] Establish the corresponding mouse tumor model, when the tumor size is about 100-200mm 3 After hours, the mice were randomly divided into control group and experimental group.

[0046] A. Control group: intravenous injection of PBS, daily injection, for 7 weeks;

[0047] B. DMF targeted therapy group: intravenous injection of self-assembled nanopeptides loaded with DMF, injected daily for 7 weeks;

[0048] The tumor volume was measured every two days, and the calculation formula was: V=1 / 2×L×W 2 , L is the longest diameter of the tumor, W is the shortest diameter of the tumor. At the same time, the body weight changes of the mice were detected.

[0049] The experimental results obtained by the above method are as follows image 3 shown. A mouse tumor model was established, and the drug was administered after the tumor grew to a certain size. The results suggest that DMF has a certain inhib...

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Abstract

The invention belongs to the field of biotechnology and medicine, and particularly relates to an application of dimethyl fumarate (DMF) in the aspects of regulating tumor metabolism and inhibiting tumor growth. The application of the DMF as a small-molecule inhibitor in the aspect of regulating the tumor metabolism so as to inhibit the tumor growth is discovered for the first time; the DMF can inhibit proliferation of various tumor cells in vitro and reduce metabolism of the tumor cells, and has a certain inhibiting effect on occurrence and development of tumors in vivo; and by inhibiting thetumor metabolism, the tumor acidic microenvironment is improved, the inhibition on the T cell functions is reduced, the T cell reactivity is improved, the immunotherapy efficiency is enhanced, and a new target and a new idea are provided for tumor treatment.

Description

technical field [0001] The invention belongs to the fields of biotechnology and medicine, in particular to the application of dimethyl fumarate DMF in regulating tumor metabolism and inhibiting tumor growth. Background technique [0002] Metabolism is the basic feature of the body's life activities and the most important way for cells to obtain energy. During the development of tumors, energy metabolism is often disordered, resulting in changes in the tumor microenvironment (TME), which helps tumor cells survive, metastasize and escape from immunity. Studies have confirmed that in some tumors, glycolysis is the main way of energy metabolism because the tumor is in a hypoxic microenvironment. In the 1930s, Dr. Otto Warburg discovered that in O 2 Under sufficient conditions, tumor cells still rely on aerobic glycolytic capacity. This phenomenon that tumor cells do not utilize mitochondrial oxidative phosphorylation capacity even under aerobic conditions, but instead utilize...

Claims

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Application Information

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IPC IPC(8): A61K31/225A61P35/00A61P37/04
CPCA61K31/225A61P35/00A61P37/04
Inventor 殷雷雷骏方嘉凌杨怡李永征
Owner WUHAN UNIV
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